Diet-induced obesity mediated through estrogen-related receptor α is independent of intestinal function

Obesity has escalated to epidemic proportions, driving significant advances in therapeutic strategies aimed at combating this condition. The estrogen-related receptor α (ESRRA), a transcription factor, plays pivotal roles in energy metabolism across multiple tissues. Research has consistently shown that the absence of Esrra results in notable fat malabsorption and increased resistance to diet-induced obesity. However, existing studies primarily focusing on germline Esrra mutants fail to account for tissue-specific roles of ESRRA in obesity. Notably, Esrra exhibits high expression in the gastrointestinal tract relative to other tissues. Given the gastrointestinal tract's central role in dietary lipid absorption and metabolism, it is critical to investigate how ESRRA specifically affects this tissue. This study aims to fill this gap by employing advanced mouse genetics and genomics techniques to dissect the impact of ESRRA within the intestine. We also aim to elucidate ESRRA's specific contributions to diet-induced obesity and refine our understanding of how this transcription factor influences metabolic outcomes in the context of dietary intake.